Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Pediatric Hematology and Oncology, Pediatrics III, University Hospital Essen, Essen, Germany.
Blood Adv. 2018 Jul 10;2(13):1532-1540. doi: 10.1182/bloodadvances.2018018945.
Approximately 5% to 10% of children with Down syndrome (DS) are diagnosed with transient myeloproliferative disorder (TMD). Approximately 20% of these patients die within 6 months (early death), and another 20% to 30% progress to myeloid leukemia (ML-DS) within their first 4 years of life. The aim of the multicenter, nonrandomized, historically controlled TMD Prevention 2007 trial was to evaluate the impact of low-dose cytarabine treatment on survival and prevention of ML-DS in patients with TMD. Patients received cytarabine (1.5 mg/kg for 7 days) in case of TMD-related symptoms at diagnosis (high white blood cell count, ascites, liver dysfunction, hydrops fetalis) or detection of minimal residual disease (MRD) 8 weeks after diagnosis. The 5-year probability of event-free and overall survival of 102 enrolled TMD patients was 72 ± 5% and 91 ± 3%, respectively. In patients eligible for treatment because of symptoms (n = 43), we observed a significantly lower cumulative incidence (CI) of early death as compared with symptomatic patients in the historical control (n = 45) (12 ± 5% vs 33 ± 7%, = .02). None of the asymptomatic patients in the current study suffered early death. However, the treatment of symptomatic or MRD-positive patients did not result in a significantly lower CI of ML-DS (25 ± 7% [treated] vs 14 ± 7% [untreated], = .34 [per protocol analysis]; historical control: 22 ± 4%, = .55). Thus, low-dose cytarabine treatment helped to reduce TMD-related mortality when compared with the historical control but was insufficient to prevent progression to ML-DS. This trial was registered at EudraCT as #2006-002962-20.
约 5%至 10%的唐氏综合征（DS）患儿被诊断为短暂性髓系增生异常（TMD）。这些患者中约 20%在 6 个月内死亡（早期死亡），另外 20%至 30%在生命的头 4 年内发展为髓系白血病（ML-DS）。多中心、非随机、历史对照 TMD Prevention 2007 试验的目的是评估低剂量阿糖胞苷治疗对 TMD 患者生存和预防 ML-DS 的影响。如果 TMD 患者出现相关症状（白细胞计数高、腹水、肝功能障碍、胎儿水肿）或在诊断后 8 周检测到微小残留病（MRD），则接受阿糖胞苷（1.5mg/kg，持续 7 天）治疗。102 名 TMD 患者的 5 年无事件生存率和总生存率分别为 72%±5%和 91%±3%。在因症状而有资格接受治疗的患者（n=43）中，与历史对照（n=45）中因症状而有资格接受治疗的患者相比，早期死亡的累积发生率（CI）显著降低（12%±5% vs 33%±7%，=0.02）。本研究中无症状患者均未发生早期死亡。然而，对有症状或 MRD 阳性的患者进行治疗并未显著降低 ML-DS 的 CI（25%±7%[治疗] vs 14%±7%[未治疗]，=0.34[按方案分析]；历史对照：22%±4%，=0.55）。因此，与历史对照相比，低剂量阿糖胞苷治疗有助于降低 TMD 相关死亡率，但不足以预防向 ML-DS 的进展。该试验在 EudraCT 中注册为 #2006-002962-20。
